Use of incremental peritoneal dialysis: impact on clinical outcomes and quality of life measure.
Incremental peritoneal dialysis (PD) can be defined as a PD prescription that is less than the standard, full dose prescription and is typically used for patients initiating PD with residual kidney function. It has been suggested that use of incremental peritoneal dialysis may help preserve residual kidney function and may offer better quality of life due to the lower treatment burden, however published evidence is limited. In this study we assessed the associations between incremental peritoneal dialysis use and both clinical outcomes and quality of life measures in a large cohort of incident peritoneal dialysis patients in the US. We considered adult patients initiating peritoneal dialysis between 31 July, 2015 and 31 May, 2019 within a single dialysis organization. Patients with body weight < 40 kg, amputation, or an estimated glomerular filtration rate > 20 mL/min during the first 4 weeks on peritoneal dialysis were excluded. Patients were assigned to exposure groups based on peritoneal dialysis prescription during dialysis weeks 5-8. Incremental peritoneal dialysis was defined by treatment frequency, number of exchanges/day, and exchange volume (for continuous ambulatory peritoneal dialysis patients) or by treatment frequency and presence/absence of last fill (for automated peritoneal dialysis patients). Analyses were performed separately for continuous ambulatory peritoneal dialysis and automated peritoneal dialysis. For each analysis, incremental peritoneal dialysis patients were propensity score matched to eligible full-dose peritoneal dialysis patients. Patients were followed for a maximum of 12 months until censoring for loss to follow-up or study end. Outcomes were compared using Poisson models (mortality, hospitalization, peritoneal dialysis discontinuation), linear mixed models (estimated glomerular filtration rate), and paired t tests (KDQOL domain scores). Among continuous ambulatory peritoneal dialysis patients, compared to full-dose peritoneal dialysis, incremental peritoneal dialysis use was associated with better KDQOL scores on 3 domains: physical composite score (42.5 vs 37.7, p = 0.03), burden of kidney disease (60.2 vs 45.6, p = 0.003), effects of kidney disease (79.4 vs 72.3, p = 0.05). Hospitalization and mortality rates were numerically lower (0.77 vs 1.12 admits/pt-year, p = 0.09 and 5.0 vs 10.2 deaths/100 pt-years, p = 0.22), while no associations were found with estimated glomerular filtration rate or peritoneal dialysis discontinuation rate. Use of incremental peritoneal dialysis was not associated with any discernable effects on outcomes in automated peritoneal dialysis patients. These results suggest that there may be benefits of using incremental PD in the context of continuous ambulatory peritoneal dialysis, particularly with respect to quality of life as a prescription strategy when initiating peritoneal dialysis. While no significant benefits of incremental peritoneal dialysis were detected among patients initiating automated peritoneal dialysis, no detrimental effects of using incremental schedules were observed for either peritoneal dialysis type.


Enhancement and suppression of tactile signals during reaching.
The perception of tactile stimuli presented on a moving hand is systematically suppressed. Such suppression has been attributed to the limited capacity of the brain to process task-irrelevant sensory information. Here, we examined whether humans do not only suppress movement-irrelevant but also enhance in parallel movement-relevant tactile signals when performing a goal-directed reaching movement. Participants reached to either a visual (LED) or somatosensory target (thumb or index finger of their unseen static hand) and discriminated 2 simultaneously presented tactile stimuli: a reference stimulus on the little finger of their static hand and a comparison stimulus on the index finger of their moving hand. Thus, during somatosensory reaching the location of the reference stimulus was task-relevant. Tactile suppression, as reflected by the increased points-of-subjective-equality (PSE) and just-noticeable-differences (JND), was stronger during reaching to somatosensory than visual targets. In Experiment 2, we presented the reference stimulus at a task-irrelevant location (sternum) and found similar suppression for somatosensory and visual reaching. This suggests that participants enhanced the sensation of the reference stimulus at the target hand during somatosensory reaching in Experiment 1. This suggestion was confirmed in Experiment 3 using a detection task in which we found lower detection thresholds on the target hand during somatosensory but not during visual reaching. We postulate that humans can flexibly modulate their tactile sensitivity by suppressing movement-irrelevant and enhancing movement-relevant signals in parallel when executing a reaching movement. (PsycINFO Database Record


IthaGenes: an interactive database for haemoglobin variations and epidemiology.
Inherited haemoglobinopathies are the most common monogenic diseases, with millions of carriers and patients worldwide. At present, we know several hundred disease-causing mutations on the globin gene clusters, in addition to numerous clinically important trans-acting disease modifiers encoded elsewhere and a multitude of polymorphisms with relevance for advanced diagnostic approaches. Moreover, new disease-linked variations are discovered every year that are not included in traditional and often functionally limited locus-specific databases. This paper presents IthaGenes, a new interactive database of haemoglobin variations, which stores information about genes and variations affecting haemoglobin disorders. In addition, IthaGenes organises phenotype, relevant publications and external links, while embedding the NCBI Sequence Viewer for graphical representation of each variation. Finally, IthaGenes is integrated with the companion tool IthaMaps for the display of corresponding epidemiological data on distribution maps. IthaGenes is incorporated in the ITHANET community portal and is free and publicly available at http://www.ithanet.eu/db/ithagenes.


Disentangling levels of mother-infant neuroendocrine attunement and longitudinal relations with maternal risk and protective factors.
Scientific understanding of mother-infant HPA axis attunement has been limited by discrepant methods for assessing attunement that often conflate different levels of association. We sought to refine the conceptualization of attunement by investigating whether mother-infant cortisol attunement exists as coupling of response trajectories within an acute stress episode, separate from shared developmental patterns and/or overall dyadic similarity in cortisol levels, and whether the degree of attunement depends on within- or between-dyad differences in maternal risk and protective factors. We examined these questions using a longitudinal study with mother/infant salivary cortisol during dyadic stressors at 6, 12, and 18 months postnatal. A three-level hierarchical linear model showed that sample-wide associations between mother and infant cortisol were not significant at any level, suggesting normative lack of attunement; however, there was significant variability in degree of attunement across dyads. Concurrent levels of family resources and social support satisfaction predicted lower mother-infant cortisol attunement within the session, and overall (mean) parenting stress predicted the opposite. Follow-up analyses showed this was typically due to an increase in infants' (but not their mothers') within-session cortisol response slopes with increasing support and decreasing stress. Implications for the role of mother-infant cortisol attunement in intergenerational stress transmission are discussed.


Urinary protein excretion and expectant management of early onset, severe pre-eclampsia.
To evaluate the importance of proteinuria in the expectant management of early onset, severe pre-eclampsia. In this prospective series of 340 women, 24-h urine collections were performed and monitored twice weekly in a high-care ward. Seventy-four women with at least two 24-h urine collections were grouped into women with a proteinuria increase of > or =2 g (n=29) and with women whose proteinuria decreased, or increased by <2 g (n=45). Major maternal complications, prolongation of gestation, and perinatal outcomes were comparable. Fifty-six (75%) women experienced an increase in proteinuria. When patients with heavy proteinuria (n=83) were compared to those with moderate proteinuria (n=257), maternal and perinatal outcomes were comparable. More days were gained before delivery in the heavy proteinuria group than in the moderate (12 vs. 9; P<0.001). Most patients experienced increased proteinuria. Neither the rate of increase nor the amount of proteinuria affected maternal and perinatal outcomes.


Egg coat proteins activate calcium entry into mouse sperm via CATSPER channels.
During mammalian fertilization, the contact between sperm and egg triggers increases in intracellular Ca(2+) concentration ([Ca(2+)](i)) in sperm. Voltage-gated Ca(2+) channels (Ca(V)s) are believed to mediate the initial phase of [Ca(2+)](i) increases in sperm induced by egg coat (zona pellucida [ZP]) glycoproteins, while store depletion-activated Ca(2+) entry is thought to mediate the sustained phase. Using patch-clamp recording and Ca(2+) imaging, we show herein that Ca(V) channel currents, while found in spermatogenic cells, are not detectable in epididymal sperm and are not essential for the ZP-induced [Ca(2+)](i) changes. Instead, CATSPER channels localized in the distal portion of sperm (the principal piece) are required for the ZP-induced [Ca(2+)](i) increases. Furthermore, the ZP-induced [Ca(2+)](i) increase starts from the sperm tail and propagates toward the head.


[Prospective feasibility study of chest X-ray vs. thoracic MRI in breath-hold technique at an open low-field scanner].
MR investigations using a breath-hold sequence at an open low-field MR had to be compared to chest X-rays in patients with a wide spectrum of cardio-thoracic pathologies. 114 patients and three volunteers who actually received a chest X-ray due to different indications underwent triplanar breath-hold (17 - 20 s) True-FISP sequence using a 0.2 T low-field MR (Siemens Magnetom Open, TR/TE/alpha: 7.3/3.5/80 degrees, SD: 10 mm, Pixel: 2.81 x 1.41 mm) a mean of 5.1 (+/- 8.2) days later. Signal-to-noise ratio as basics for pattern recognition was 3.2 in nodule, 5.0 in infiltration, and 12.0 in effusion, and therefore True-FISP is usable for the detection of these findings. MRI demonstrated nodules (89 % vs. 57 %), infiltration (81 % vs. 71 %), pleural effusions (86 % vs. 75 %), pericardial effusions (100 % vs. 21 %) and pulmonary congestion (90 % vs. 80 %) clearly more frequently compared to chest X-ray. MRI of the lung has been implemented successfully at an open low-field MR system. Diagnostic safety and accuracy are at least comparable to those of chest X-ray. The lack of superimposition led to a major improvement in the detection of pericardial effusions and nodules, and an increase in identification of infiltration, pleural effusion, and pulmonary congestion.


Microarray analysis of Myf5-/-:MyoD-/- hypoplastic mouse lungs reveals a profile of genes involved in pneumocyte differentiation.
Fetal breathing-like movements (FBMs) are important in normal lung growth and pneumocyte differentiation. In amyogenic mouse embryos (designated as Myf5-/-:MyoD-/-, entirely lacking skeletal musculature and FBMs), type II pneumocytes fail to differentiate into type I pneumocytes, the cells responsible for gas exchange, and the fetuses die from asphyxia at birth. Using oligonucleotide microarrays, we compared gene expression in the lungs of Myf5-/-:MyoD-/- embryos to that in normal lungs at term. Nine genes were found to be up-regulated and 54 down-regulated at least 2-fold in the lungs of double-mutant embryos. Since many down-regulated genes are involved in lymphocyte function, immunohistochemistry was employed to study T- and B-cell maturity in the thymus and spleen. Our findings of normal lymphocyte maturity implied that the down-regulation was specific to the double-mutant lung phenotype and not to its immune system. Immunostaining also revealed altered distribution of transcription and growth factors (SATB1, c-Myb, CTGF) from down-regulated genes whose knockouts are now known to undergo embryonic or neonatal death secondary to respiratory failure. Together, it appears that microarray analysis has identified a profile of genes potentially involved in pneumocyte differentiation and therefore in the mechanisms that may be implicated in the mechanochemical signal transduction pathways underlying FBMs-dependent pulmonary hypoplasia.


Neuroprotection conferred by post-ischemia ethanol therapy in experimental stroke: an inhibitory effect on hyperglycolysis and NADPH oxidase activation.
Ethanol provides neuroprotection following ischemia/reperfusion. This study assessed ethanol's effect on hyperglycolysis and NADPH oxidase (NOX) activation. Adult, male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Three sets of experiments were conducted to determine ethanol's effect on (i) conferring neuroprotection by measuring infarct volume and neurological deficits 24 h post reperfusion; (ii) cerebral glucose metabolism and lactic acidosis by measuring brain and blood glucose concentrations and protein expression of glucose transporter 1 and 3 (GLUT1, GLUT3), phosphofructokinase (PFK), as well as lactic acidosis by measuring lactate dehydrogenase (LDH), and lactate; and (iii) nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activation by detecting enzymatic activity and subunit expression at 3 h after reperfusion. When administered upon reperfusion, ethanol (1.5 g/kg) reduced infarct volume by 40% (p < 0.01) and neurological deficits by 48% at 24 h post reperfusion while reducing (p < 0.01) elevations in glycolytic protein expression and lactate levels during early reperfusion (3 h). Ethanol increased the reductions in cerebral glucose concentration at 3 h post reperfusion by 64% (p < 0.01) while enhancing (p < 0.01) post stroke blood glucose concentration, suggesting a reduced cellular glucose uptake and utilization. Ethanol decreased (p < 0.01) stroke-induced NOX activation by reducing enzymatic activity and gp91(phox) expression by 45% and 38%, respectively. Post-ischemia ethanol treatment exerts neuroprotection through attenuation of hyperglycolysis and associated NOX activation. Because of the lack of associated hypoglycemia and selectivity toward decreasing cerebral metabolism, further investigation of ethanol's use as a post-stroke therapy, especially in the context of hyperglycemia, seems warranted.


How inhibitory and excitatory inputs gate output of the inferior olive.
The inferior olive provides the climbing fibers to Purkinje cells in the cerebellar cortex, where they elicit all-or-none complex spikes and control major forms of plasticity. Given their important role in both short-term and long-term coordination of cerebellum-dependent behaviors, it is paramount to understand the factors that determine the output of olivary neurons. Here, we use mouse models to investigate how the inhibitory and excitatory inputs to the olivary neurons interact with each other, generating spiking patterns of olivary neurons that align with their intrinsic oscillations. Using dual color optogenetic stimulation and whole-cell recordings, we demonstrate how intervals between the inhibitory input from the cerebellar nuclei and excitatory input from the mesodiencephalic junction affect phase and gain of the olivary output at both the sub- and suprathreshold level. When the excitatory input is activated shortly (~50 ms) after the inhibitory input, the phase of the intrinsic oscillations becomes remarkably unstable and the excitatory input can hardly generate any olivary spike. Instead, when the excitatory input is activated one cycle (~150 ms) after the inhibitory input, the excitatory input can optimally drive olivary spiking, riding on top of the first cycle of the subthreshold oscillations that have been powerfully reset by the preceding inhibitory input. Simulations of a large-scale network model of the inferior olive highlight to what extent the synaptic interactions penetrate in the neuropil, generating quasi-oscillatory spiking patterns in large parts of the olivary subnuclei, the size of which also depends on the relative timing of the inhibitory and excitatory inputs.


Reactivation of chronic hepatitis B virus infection by cancer chemotherapy.
Two patients referred for cancer chemotherapy were found to be chronic, asymptomatic hepatitis B surface antigen (HBsAg) carriers. They had normal serum aminotransferase levels, but their sera were positive for HGsAg and antibody to hepatitis B e antigen. Both patients developed acute, icteric hepatitis within 3 months of starting cycled chemotherapy. In both cases, the disease seemed to be caused by a recurrence of type B hepatitis; it was accompanied by a marked increase in HBsAg titer and the appearance of hepatitis B virus DNA and DNA polymerase in the serum. One patient had a second episode of acute hepatitis after a second course of chemotherapy, but both patients ultimately recovered and became seronegative for HBsAg. Thus, it seems that cancer chemotherapeutic agents can reactivate type B hepatitis in asymptomatic HBsAg carriers. This reactivation is most likely due to an increase in hepatitis B virus synthesis followed by a rebound in host immune responses to hepatitis B virus infection when therapy is stopped. Such a phenomenon could have important implications for the therapy of chronic hepatitis B virus infection.


Angiotensin-converting enzyme 2 (ACE2) levels in relation to risk factors for COVID-19 in two large cohorts of patients with atrial fibrillation.
The global COVID-19 pandemic is caused by the SARS-CoV-2 virus entering human cells using angiotensin-converting enzyme 2 (ACE2) as a cell surface receptor. ACE2 is shed to the circulation, and a higher plasma level of soluble ACE2 (sACE2) might reflect a higher cellular expression of ACE2. The present study explored the associations between sACE2 and clinical factors, cardiovascular biomarkers, and genetic variability. Plasma and DNA samples were obtained from two international cohorts of elderly patients with atrial fibrillation (n = 3999 and n = 1088). The sACE2 protein level was measured by the Olink Proteomics® Multiplex CVD II96 × 96 panel. Levels of the biomarkers high-sensitive cardiac troponin T (hs-cTnT), N-terminal probrain natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), C-reactive protein, interleukin-6, D-dimer, and cystatin-C were determined by immunoassays. Genome-wide association studies were performed by Illumina chips. Higher levels of sACE2 were statistically significantly associated with male sex, cardiovascular disease, diabetes, and older age. The sACE2 level was most strongly associated with the levels of GDF-15, NT-proBNP, and hs-cTnT. When adjusting for these biomarkers, only male sex remained associated with sACE2. We found no statistically significant genetic regulation of the sACE2 level. Male sex and clinical or biomarker indicators of biological ageing, cardiovascular disease, and diabetes are associated with higher sACE2 levels. The levels of GDF-15 and NT-proBNP, which are associated both with the sACE2 level and a higher risk for mortality and cardiovascular disease, might contribute to better identification of risk for severe COVID-19 infection.


Sexual revictimization: a review of the empirical literature.
This article reviews the literature on sexual revictimization, covering approximately 90 empirical studies and includes a discussion of prevalence, risk factors, and correlates of sexual revictimization. Research suggests that two of three individuals who are sexually victimized will be revictimized. The occurrence of childhood sexual abuse and its severity are the best documented and researched predictors of sexual revictimization. Multiple traumas, especially childhood physical abuse, and recency of sexual victimization are also associated with higher risk. There is preliminary evidence that membership in some ethnic groups or coming from a dysfunctional family places an individual at a greater risk. Revictimization is associated with higher distress and certain psychiatric disorders. People who were revictimized show difficulty in interpersonal relationships, coping, self-representations, and affect regulation and exhibit greater self-blame and shame. Existing research on prevention efforts and treatment is discussed. More longitudinal studies on sexual revictimization are needed.


A linear mixed model for predicting a binary event from longitudinal data under random effects misspecification.
The use of longitudinal data for predicting a subsequent binary event is often the focus of diagnostic studies. This is particularly important in obstetrics, where ultrasound measurements taken during fetal development may be useful for predicting various poor pregnancy outcomes. We propose a modeling framework for predicting a binary event from longitudinal measurements where a shared random effect links the two processes together. Under a Gaussian random effects assumption, the approach is simple to implement with standard statistical software. Using asymptotic and simulation results, we show that estimates of predictive accuracy under a Gaussian random effects distribution are robust to severe misspecification of this distribution. However, under some circumstances, estimates of individual risk may be sensitive to severe random effects misspecification. We illustrate the methodology with data from a longitudinal fetal growth study.


Intermittent feeding and fasting reduces diabetes incidence in BB rats.
Food intake may be one of several factors which influence the risk of development of insulin dependent diabetes mellitus, but the influence of the pattern of food supply has not been studied previously. The aim of the present study was to investigate the effect of intermittent feeding and fasting upon diabetes in BB rats. This study included three groups. Group 1 served as control and included 77 animals, 79% became diabetic. In groups 2 and 3, after weaning, food but not water was withdrawn from the animals: 24 h twice a week in group 2; 24 h every second day in group 3. Group 2 included 40 BB rats, 50% (p < 0.004) became diabetic. Group 3 included 44 BB rats, 52% (p < 0.01) became diabetic. No differences were seen between sexes. Degree of insulitis was not influenced by changed food supply. Regarding blood glucose, no influence was seen among diabetic animals, among non-diabetic animals changed food supply reduced blood glucose values obtained at the end of the study. Intermittent feeding and fasting tended to reduce mean age at the time of diagnosis of diabetes, significance was reached only in female animals from group 3 compared to group 1. Body weight was obtained weekly. Intermittent feeding and fasting caused a reduced weight gain in group 2 as well as in group 3 compared to control animals; however, most pronounced in group 3 and also more pronounced among males compared to females. For pre-diabetic and non-diabetic animals comparable influence on body weight was seen. The main conclusion in the study is that intermittent feeding and fasting reduced diabetes incidence in BB rats.


Implications of seismic and GNSS strain rates in Himachal, Kashmir and Ladakh.
We report the present day GNSS velocities (2015-2021) and strain rates in Himachal, Kashmir and Ladakh Himalaya covering the rupture zones of the 2005 Muzaffarabad earthquake and the 1905 Kangra earthquake. Geodetic strain rates estimated from GPS velocities of about 58 sites spanning last two decades of measurements indicate a mean compression rate of - 32.5 ns/year (nanostrain/year) and dilatation of - 37.3 ns/year. Seismic strain rates are estimated using both the instrumental period (1964-2021) and historical earthquakes since 1500 AD in this region. Seismic strain rates during the instrumental period of the past 50 + years indicate a mean compression rate of - 28.1 ns/year and it slightly decreases to - 21.7 ns/year after including the historical earthquakes of the past 520 years. The Azimuth of the seismic strain tensor for the instrumental and historic periods and geodetic strain tensor is broadly consistent with orientation of major faulting in this region suggesting uniform compression over a long-time interval justifying combined analysis of the strain rate field to determine the seismic potential of the region. Composite analysis of geodetic and seismic strain rates and the associated moments estimate the accumulated strain budget of ~ 1E + 21 Nm in the past 520 years which has a potential of generating future earthquake of Mw > 8 in this segment of Northwest Himalaya.


Toward an integrative model of transdiagnostic risk factors and suicide: A network comparison of psychiatric outpatients.
Predictive models using traditional statistical methods have largely failed to describe suicide etiology. Network theory, which conceptualizes factors as mutually interacting, reinforcing elements of a complex outcome, can model relationships between transdiagnostic and neurocognitive vulnerability factors. The present study used a network approach to produce an atheoretical model of psychological factors and their interrelationships within a population of ideators and non-ideators. We developed two network models (i.e., suicidal ideators and psychiatric controls) describing the relationships between a diverse set of risk factors and symptom measures for a population of psychiatric outpatients. We compared networks using three measures of network structure (i.e., network structure invariance, global strength invariance, edge invariance) and described the differences. Network structures for ideators (N = 229) and non-ideators (N = 454) were stable and accurate. In non-ideators, cognitive-affective depression symptoms (Expected Influence [EI]: 2.06), trauma avoidance (EI: 1.08), and negative affect (EI: 0.81) were most influential to the psychological network. In ideators, cognitive-affective depression symptoms (EI: 1.77), intolerance of uncertainty-negative self-referent implications (EI: 1.29), and negative affect (EI: 1.19) were most influential. Invariance testing did not indicate significant differences in overall network structure between ideators and non-ideators (p = .111), but did indicate significant differences in node strength (p = .013). Significant differences in node EI were detected for intolerance of uncertainty-negative self-referent implications, anxiety sensitivity physical concerns, thwarted belongingness, worry, and negative affect. These findings indicated differences in network structures for suicidal psychiatric outpatients and provide crucial directions for future research on therapeutic targets for suicidal thoughts and behaviors.


Fracture repair with ultrasound: clinical and cell-based evaluation.
Fracture repair continues to be widely investigated, both within the clinical realm and at the fundamental research level, in part due to the fact that 5% to 10% of fractures result in either delayed union or nonunion, depending on the duration of incomplete healing. Beyond the temporal delay in repair, nonunions share the same unifying characteristic: all periosteal and endosteal repair processes have stopped and the fracture will not heal without surgical intervention. A less-invasive alternative method--low-intensity pulsed ultrasound--has shown promise as a treatment for delayed unions and nonunions and as a method to facilitate distraction osteogenesis. In this paper, we summarize the clinical effectiveness of low-intensity pulsed ultrasound with regard to fracture repair, treatment of nonunion, and distraction osteogenesis and we discuss the results of a multitude of published studies that have sought to elucidate the mechanisms behind that effectiveness through research on low-intensity pulsed ultrasound exposure on osteoblasts and osteoblast precursors. When evaluated clinically, low-intensity pulsed ultrasound was shown to enhance bone repair (most commonly noted as a decrease in healing time), although variations in patient population hindered a definitive claim to clinical effectiveness. In vitro cellular evaluation and in vivo studies on animal models have revealed an increase in cell proliferation, protein synthesis, collagen synthesis, membrane permeability, integrin expression, and increased cytosolic Ca(2+) levels as well as other increased indicators of bone repair in response to low-intensity pulsed ultrasound exposure. Many of the cellular responses to low-intensity pulsed ultrasound mirror the cellular responses to fluid-induced shear flow, suggesting a link between the two as one potential mechanism of action. The considerable amount of information that has been revealed about the behavior of osteoblasts under low-intensity pulsed ultrasound exposure suggests that the exact mechanism of action is complex. It is clear, however, that considerable progress is being made toward uncovering these mechanisms, which has served to encourage the use of low-intensity pulsed ultrasound in new applications. It is posited that successful noninvasive treatment strategies such as low-intensity pulsed ultrasound may be combined with other conventional and novel tissue-regeneration strategies to develop new treatments for large-scale bone defects.


Quality of counselling of young clients in Zimbabwe.
Researchers observed 418 consultations with clients aged 12-24 years at 38 health facilities throughout Zimbabwe and interviewed both the clients and providers. Less than one per cent of clients at these facilities were aged 12-14 years; between 5% and 20% were aged 15-19 years. Compared with older clients, those aged 12-16 years came more often for antenatal care and medical problems and less often for family planning. In sessions with 12-16 years, the most common topics were STDs (48%) and school (46%), while sessions with older clients focused more on family planning (56-68%). Providers rarely discussed adolescence or non-sexual problems such as alcohol and drugs. Younger clients were less likely than older clients to ask questions without prompting (16%), expressed their concerns (27%), and they were more likely to appear embarrassed (58%) and shy (64%). Most service providers believed that the parents should be notified if a young, unmarried client was pregnant (89%), had HIV/AIDS (74%), or engaged in sex at "an early" age (73%). The findings suggest that young people may be reluctant to seek advice at health facilities because of legitimate concerns about privacy, providers' attitudes, and narrow focus on reproductive health.


Attitudes of faculty, housestaff, and medical students toward clinical practice guidelines.
To examine attitudes of faculty, housestaff, and medical students toward clinical practice guidelines. In a 1997 cross-sectional survey, a two-part, 26-item, self-administered questionnaire was mailed to all faculty, housestaff, and medical students in the department of internal medicine at Case Western Reserve University School of Medicine. The questionnaire asked for demographic information and attitudes toward clinical guidelines. Of 379 persons surveyed, 254 (67%) returned usable questionnaires: 56% of the medical students, 70% of the housestaff, and 73% of the full-time faculty. Medical students reported learning about guidelines predominantly during clerkships in internal medicine (71%) and pediatrics (68%). Overall, the respondents agreed most strongly that guidelines are "useful for the care of common problems," and least strongly that guidelines are "difficult to apply to individual patients" and "reduce physician options in patient care." Faculty were more likely to consider guidelines a "good educational tool" and less likely than were medical students and housestaff to agree that they promote "cookbook medicine." Of 11 influences on clinical decision making, the three groups together rated practice guidelines eighth or ninth. The use of guidelines for academic investigations was rated most appropriate, overall. In terms of their appropriateness, faculty consistently rated the use of guidelines more favorably except for use in malpractice suits. Faculty, housestaff, and medical students have significantly different perceptions of and attitudes toward clinical practice guidelines. Further studies are needed to explain the reasons for these differences. Considerable education and involvement must occur at all levels for practice guidelines to be successfully implemented and understood.


Tuning up microbiome analysis to monitor WWTPs' biological reactors functioning.
Wastewater treatment plants (WWTPs) are necessary to protect ecosystems quality and human health. Their function relies on the degradation of organic matter and nutrients from a water influent, prior to the effluent release into the environment. In this work we studied the bacterial community dynamics of a municipal WWTP with a membrane bioreactor through 16S rRNA gene sequencing. The main phyla identified in the wastewater were Proteobacteria, Bacteroidetes, Chloroflexi, Planctomycetes and Actinobacteria. The WWTP is located in Spain and, like other studied WWTP in temperate climate zones, the temperature played a major role in community assembly. Seasonal community succession is observed along the two years sampling period, in addition to a continual annual drift in the microbial populations. The core community of the WWTP bioreactor was also studied, where a small fraction of sequence variants constituted a large fraction of the total abundance. This core microbiome stability along the sampling period and the likewise dissimilarity patterns along the temperature gradient makes this feature a good candidate for a new process control in WWTPs.


Nuanced relations between simultaneous alcohol and cannabis use motives and negative consequences among college students: The role of multiple product use.
Simultaneous alcohol and marijuana (SAM) use is common, but it exacerbates negative consequences. Individuals use alcohol and cannabis products in different ways and have distinct reasons for use. The present study examines day-level effects of motives on consequences on SAM-use days, accounting for consumption, and tests whether using multiple alcohol (e.g., beer + liquor) and/or cannabis (e.g., concentrate + leaf) products on the same day mediates these relations. College students engaging in SAM use at least once in the past month (N = 281; Mage = 20.17) completed two bursts of 28 consecutive days of data collection. We examined within-person effects of motives (effect-enhancement, social, offered [it was offered], coping) on number of negative consequences and on experiencing hangover, nausea, or blackout; and indirect effects via two concurrent mediators: using multiple alcohol products and multiple cannabis products. Total effect models showed effect-enhancement motives were related to nausea, social motives to number of total consequences and hangover, and coping motives to blackout. Effect-enhancement, social, and offered motives evinced significant indirect effects on consequence outcomes via multiple alcohol, but not cannabis, product use. Coping motives did not exhibit significant indirect effects, and were related to multiple cannabis, but not alcohol, product use, although all other motives were related to both mediators. Findings support recent work demonstrating within-person relations between social motives and negative consequences on SAM-use days. Limiting the number of alcohol products consumed on SAM-use days may be beneficial, particularly for young adults using to enhance intoxication or for social reasons. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Cholesterol metabolism and aging.
Changes occur in lipid and lipoprotein concentrations with age that increase the risk of developing atherosclerotic disease. In children and young adults (less than 20 years of age), the plasma total cholesterol concentration decreases between the ages of 10 and 20 years. After age 20, the plasma total cholesterol concentration increases progressively, and in men reaches a plateau between the ages of 50 and 60 years, whereas in women, it reaches a peak between 60 and 70 years of age. The low-density lipoprotein cholesterol concentration increases progressively in men and women after age 20, but more rapidly in men, accounting for most of the overall gender difference in total cholesterol. The rate at which the low-density lipoprotein cholesterol concentration increases in women begins to accelerate between 40 and 50 years of age, and the concentration exceeds that in men by 55 to 60 years. High-density lipoprotein cholesterol concentrations decrease in males during puberty and early adulthood, and thereafter remain lower than those in women at all comparable ages. The high-density lipoprotein cholesterol concentrations remain constant in women throughout their lifetime. Beyond 30 years of age, women taking estrogen preparations have higher high-density lipoprotein cholesterol concentrations than women who are not taking estrogens. The triglyceride concentration increases progressively in men, reaching peak values between 40 and 50 years of age, and then declining slightly thereafter. In women, the triglyceride concentration increases throughout their lifetime, but is always higher in those using estrogens. Whether these changes in lipoprotein concentrations merely accompany the increasing prevalence of atherosclerotic vascular disease that occurs with age, or contribute to it, is unknown at this time.


Using viral vectors to silence endogenous genes.
Virus-induced gene silencing (VIGS) is a fast but transient method for knocking down expression of endogenous genes in plants. Replicating plant viruses activate a defense mechanism called post-transcriptional gene silencing (PTGS), which protects the plant by silencing viral transcripts. VIGS of endogenous genes is accomplished by inserting a gene of interest into a viral vector. When the virus replicates in the plant, PTGS silences both the viral genome and the corresponding endogenous gene. The most robust and widely implemented VIGS system uses tobacco rattle virus (TRV) vectors and N. benthamiana as the plant host. This unit will explain how to introduce TRV-based VIGS vectors into N. benthamiana plants by two methods: syringe infiltration or the Agrobacterium drench method. Furthermore, it will provide two alternate protocols optimized for VIGS in tomato plants: spray inoculation and vacuum infiltration.


An algorithm for the detection of individual breaths from the pulse oximeter waveform.
To determine if wavelet analysis techniques can be used to reliably identify individual breaths from the photoplethysmogram (PPG). Photoplethysmograms were obtained from 22 healthy adult volunteers timing their respiration rate in synchronisation with a metronome. A secondary timing signal was obtained by asking the volunteers to actuate a small push button switch, held in their right hand, in synchronisation with their respiration. Each PPG was analyzed using primary wavelet decomposition and two new, related, secondary decompositions to determine the accuracy of individual breath detection. The optimal breath capture was obtained by manually polling the three techniques, allowing detection of 466 out of the 472 breaths studied; a detection rate of 98.7% with no false positive breaths detected. Our technique allows the accurate capture of individual breaths from the photoplethysmogram, and leads the way for developing a simple non-invasive combined respiration and saturation monitor.


Ultraviolet-B exposure and exogenous hydrogen peroxide application lead to cross-tolerance toward drought in Nicotiana tabacum L.
Acclimation of plants to water deficit involves biochemical and physiological adjustments. Here, we studied how ultraviolet (UV)-B exposure and exogenously applied hydrogen peroxide (H2 O2 ) potentiates drought tolerance in tobacco (Nicotiana tabacum L. cv. xanthi nc). Separate and combined applications for 14 days of 1.75 kJ m-2 day-1 UV-B radiation and 0.2 mM H2 O2 were assessed. Both factors, individually and combined, resulted in inhibition of growth. Furthermore, the combined treatment led to the most compacted plants. UV-B- and UV-B + H2 O2 -treated plants increased total antioxidant capacity and foliar epidermal flavonol index. H2 O2 - and UV-B + H2 O2 -pre-treated plants showed cross-tolerance to a subsequent 7-day moderate drought treatment, which was assessed as the absence of negative impact on growth, leaf wilting, and leaf relative water content. Plant responses to the pre-treatment were notably different: (1) H2 O2 increased the activity of catalase (EC 220.127.116.11), phenylalanine ammonia lyase (EC 18.104.22.168), and peroxidase activities (EC 184.108.40.206), and (2) the combined treatment induced epidermal flavonols which were key to drought tolerance. We report synergistic effects of UV-B and H2 O2 on transcription accumulation of UV RESISTANCE LOCUS 8, NAC DOMAIN PROTEIN 13 (NAC13), and BRI1-EMS-SUPPRESSOR 1 (BES1). Our data demonstrate a pre-treatment-dependent response to drought for NAC13, BES1, and CHALCONE SYNTHASE transcript accumulation. This study highlights the potential of combining UV-B and H2 O2 to improve drought tolerance which could become a useful tool to reduce water use.


Protective effect of alpha-tocopherol-6-O-phosphate against ultraviolet B-induced damage in cultured mouse skin.
The ability of the novel water-soluble provitamin E, alpha-tocopherol-6-O-phosphate, to protect against ultraviolet B-induced damage in cultured mouse skin was investigated and compared with the protectiveness of alpha-tocopherol acetate in cultured mouse skin. Pretreatment of skin with 0.5% (9.4 mM) alpha-tocopherol-6-O-phosphate in medium for 3 h significantly prevented such photodamage as sunburn cell formation, DNA degradation, and lipid peroxidation, which were induced in control cultured skin by a single dose of ultraviolet B irradiation at 0 to 40 kJ per m2 (290-380 nm, maximum 312 nm). This protection was greater than that seen with alpha-tocopherol acetate, the most common provitamin E that is used in commercial human skin care products. The concentration of alpha-tocopherol in cultured skin pretreated with 0.5% alpha-tocopherol-6-O-phosphate rose to approximately two to three times that found in the control skin and the reduction in cutaneous alpha-tocopherol that was induced by ultraviolet irradiation was significantly inhibited. In the group pretreated with 0.5% alpha-tocopherol acetate, however, conversion of alpha-tocopherol acetate to alpha-tocopherol was not observed, although the level of provitamin incorporated into the cultured skin was the same as that for alpha-tocopherol-6-O-phosphate. These findings indicated that the enhanced ability of alpha-tocopherol-6-O-phosphate to protect against ultraviolet B-induced skin damage compared with alpha-tocopherol acetate may have been due to alpha-tocopherol-6-O-phosphate's conversion to alpha-tocopherol. Moreover, following pretreatment with a 0.5% alpha-tocopherol-6-O-phosphate, alpha-tocopherol-6-O-phosphate was incorporated into the human skin in a three-dimensional model and 5% of the incorporated alpha-tocopherol-6-O-phosphate was converted to alpha-tocopherol. These results suggest that treatment with the novel provitamin E, alpha-tocopherol-6-O-phosphate may be useful in preventing ultraviolet-induced human skin damage.


Comparison of glycolysis and glutaminolysis in Onchocerca volvulus and Brugia pahangi by 13C nuclear magnetic resonance spectroscopy.
Comparison of glycolysis in Brugia pahangi and Onchocerca volvulus by 13C nuclear magnetic resonance (NMR) spectroscopy showed that the former organism is predominantly a lactate fermenter and the latter resembles more closely the metabolism of a mixed acid fermenter producing lactate, succinate, acetate, ethanol, formate and carbon dioxide. Both organisms synthesize glycogen as a storage carbohydrate. Glutaminolysis in both organisms proceeds by the delta-amino-butyrate shunt to produce succinate which is then further metabolized to acetate and carbon dioxide as end-products.


Aspirin Improves Nonalcoholic Fatty Liver Disease and Atherosclerosis through Regulation of the PPARδ-AMPK-PGC-1α Pathway in Dyslipidemic Conditions.
This study is aimed at elucidating how aspirin could systemically and simultaneously normalize nonalcoholic fatty liver disease (NAFLD) and atherosclerosis through both in vitro and in vivo studies in hyperlipidemic conditions. We evaluated the effects and mechanism of aspirin on the levels of various biomarkers related to NAFLD, atherosclerosis, and oxidative phosphorylation in cells and animals of hyperlipidemic conditions. The protein levels of biomarkers (PPARδ, AMPK, and PGC-1α) involved in oxidative phosphorylation in both the vascular endothelial and liver cells were elevated by the aspirin in hyperlipidemic condition. Also in the stimulation pathway of oxidative phosphorylation by aspirin, PPARδ was a superior regulator than AMPK and PGC-1α in HepG2 cells. In the vascular endothelial cells, the phosphorylated endothelial nitric oxide synthase level was increased by the treatment. The protein levels of biomarkers related to lipid synthesis were decreased by the treatment in the liver cells. In rabbits administered with cholesterol diet, the levels of triglyceride, HDL-cholesterol, and alanine amino transferase in serums were ameliorated by the aspirin treatment, the levels of ATP and TNFα were increased or decreased, respectively, by the aspirin in liver and aorta tissues, and mannose receptor and C-C chemokine receptor type 2 levels were increased or decreased by the aspirin in spleen, respectively. The elevated levels of macrophage antigen, angiotensin II type1 receptor, and lipid accumulation were decreased in both the liver and aorta tissues in the aspirin-treated group. In conclusion, aspirin can systemically and simultaneously ameliorate NAFLD and atherosclerosis by inhibiting lipid biosynthesis and inflammation and by elevating catabolic metabolism through the activation of the PPARδ-AMPK-PGC-1α pathway. Furthermore, aspirin may normalize atherosclerosis and NAFLD by modulating the mannose receptor and CCR2 in macrophages.


Effects of progressive depletion of TCM1 or CYH2 mRNA on Saccharomyces cerevisiae ribosomal protein accumulation.
When present in excess, the mRNAs for Saccharomyces cerevisiae ribosomal proteins L3 and L29 are translated less efficiently, so that synthesis of these proteins remains commensurate with that of other ribosomal proteins (N.J. Pearson, H.M. Fried, and J.R. Warner, Cell 29:347-355, 1982; J.R. Warner, G. Mitra, W.F. Schwindinger, M. Studeny, and H.M. Fried, Mol. Cell. Biol. 5:1512-1521, 1985). We used a yeast strain with a conditionally transcribed derivative of the L3 gene to deplete cells progressively of L3 mRNA. In this case translation of L3 mRNA did not become more efficient so that L3 was not maintained at a normal level. Even when there was an initial excess of L3 mRNA, interruption of its further transcription produced an immediate drop in L3 synthesis, suggesting that the translational efficiency of preexisting mRNA cannot be altered. Lack of L3 synthesis afforded an opportunity to examine coordinate accumulation of other ribosomal proteins. Without L3, apparent synthesis of several 60S subunit proteins diminished, and 60S subunits did not assemble. A similar phenomenon occurred when, in a second strain, synthesis of ribosomal protein L29 was prevented. Loss of 60S subunit assembly was accompanied by a destabilization of some 60S ribosomal protein mRNAs. These data suggest that synthesis of some S. cerevisiae ribosomal proteins may be regulated posttranscriptionally as a function of the extent to which they are assembled.


Effect of patient-reported outcomes as a dialogue-based tool in cancer consultations on patient self-management and health-related quality of life: a clinical, controlled trial.
With increased survival among patients with metastatic melanoma and limited time with health care providers, patients are expected to assume a more active role in managing their treatment and care. Activated patients have the knowledge, skills, and confidence to make effective solutions to self-manage health. The use of patient-reported outcomes (PRO) could have the potential to enhance patient activation. However, PRO-based interventions that facilitate an activation in patients with metastatic melanoma are lacking and warranted. In this prospective non-randomized controlled, clinical trial, patients with metastatic melanoma were assigned to either the intervention (systematic feedback and discussion of PRO during consultation) given at one hospital or the control group (treatment as usual) if they received treatment from two other hospitals in Denmark. The primary outcome was the patient activation measure (PAM), which reflects self-management. Secondary outcomes were health-related quality of life (HRQoL), self-efficacy, and Patient-Physician interaction. Outcomes were measured at baseline, and after 3, 6, and 12 months. The analysis of the effect from baseline to 12 months employed mixed-effects modeling. Between 2017 and 2019, patients were allocated to either the intervention group (n = 137) or the control group (n = 142). We found no significant difference in the course of patient activation between the two groups over time. The course of HRQoL was statistically significantly improved by the intervention compared to the control group. Especially, females in the intervention group performed better than males. The other secondary outcomes were not improved by the intervention. The intervention did not improve knowledge, skills, and confidence for self-management for patients with metastatic melanoma. Neither did it improve coping self-efficacy nor perceived efficacy in Patient-Physician interaction. However, the results suggest that the intervention can have a significant impact on HRQoL and in particular social and emotional well-being among the females.


Women's empowerment and gender equality in agricultural value chains: evidence from four countries in Asia and Africa.
Women play important roles at different nodes of both agricultural and off-farm value chains, but in many countries their contributions are either underestimated or limited by prevailing societal norms or gender-specific barriers. We use primary data collected in Asia (Bangladesh, Philippines) and Africa (Benin, Malawi) to examine the relationships between women's empowerment, gender equality, and participation in a variety of local agricultural value chains that comprise the food system. We find that the value chain and the specific node of engagement matter, as do other individual and household characteristics, but in different ways depending on country context. Entrepreneurship-often engaged in by wealthier households with greater ability to take risks-is not necessarily empowering for women; nor is household wealth, as proxied by their asset ownership. Increased involvement in the market is not necessarily correlated with greater gender equality. Education is positively correlated with higher empowerment of both men and women, but the strength of this association varies. Training and extension services are generally positively associated with empowerment but could also exacerbate the inequality in empowerment between men and women in the same household. All in all, culture and context determine whether participation in value chains-and which node of the value chain-is empowering. In designing food systems interventions, care should be taken to consider the social and cultural contexts in which these food systems operate, so that interventions do not exacerbate existing gender inequalities.


Effect of nonspecific stimulation on the defense mechanisms of inbred mice.
Acquired resistance to facultative intracellular parasites was investigated in C57BL/6J inbred mice susceptibe to Salmonella typhimurium but inherently resistant to Listeria monocytogenes and in A/J inbred mice which showed the reverse relationship. A/J but not C57BL/6J mice were protected against S. typhimurium challenge by S. typhimurium phenol vaccine, S. typhimurium purified RNA, or L. monocytogenes purified RNA. C57BL/6J but not A/J could be protected against L. monocytogenes challenge by L. monocytogenes phenol vaccine, S. typhimurium RNA, or L. monocytogenes RNA. Yeast RNA, calf thymus RNA, BCG and poly (I:C) protected A/J against Salmonella and C57BL/6J against Listeria challenge. Enumeration of viable organisms in the RNA and BCG-stimulated animals after challenge indicated that macrophage activation had probably taken place. The RNA-elicited protection was long lasting and waned after about 60 days. Enhanced resistance to S. typhimurium and L. monocytogenes can be stimulated by nonliving substances bearing no known antigenic relationship to the pathogen. Enhanced resistance is elicited only in the host with a background of inherent resistance to the specific pathogen.


Strategies for Recruitment of Healthy Premenopausal Women into the African American Nutrition for Life (A NULIFE) Study.
Although African American women have an overall lower incidence of breast cancer, African American women <40 years of age are more likely than Caucasian women of all ages and postmenopausal African American women to be diagnosed with breast cancer and exhibit tumor characteristics associated with poorer survival. To begin to address this disparity, studies must be conducted to examine breast cancer preventive factors in this subpopulation of women. However, the strategies needed to recruit younger African American women have not been well defined. In this study, we assessed methods used for recruiting and retaining healthy premenopausal African American women into the African American Nutrition for Life (A NULIFE) Study. The number of women contacted, enrolled, and retained by each recruitment strategy and the efficiency of individual strategies were calculated. Overall, recruitment through social networking was most effective in contacting large numbers of healthy premenopausal African American women. The worksite recruitment method was the most efficient recruitment strategy employed, with a ratio of 40%. The study participants (n = 164) were more likely to be >or=35 years of age and have completed some college. Additionally, the interpersonal relationships recruitment approach proved most efficient (33%) in retaining participants who completed the yearlong study. The findings from this study add to the evolving research literature on minority recruitment strategies for research studies but specifically address effective recruitment of healthy young premenopausal African American women. The results demonstrate the need to use multiple recruitment strategies when recruiting this subgroup of African American women.


Consistency of adults' earliest memories across two years.
The consistency of earliest memories in content, dating, and memory qualities was investigated. A total of 84 (27 males; Mage = 24.93, SD = 1.36) adults reported earliest memories, estimated ages, and rated their recollections on memory qualities with a two-year time lag. At Time 2, their original reports at Time 1 were presented and they were asked to report whether the earliest memories they recalled at Time 2 were the same. Fifty-six per cent of the participants reported the same earliest memories and those remembering the same events had earlier memories than those remembering different ones. Although no significant differences were observed in estimated ages on the basis of mean ages, a predating bias of later memories and a tendency to postdate earlier memories were observed on the basis of a 48-month cut-off point. Thus, how the data is analysed is critical in detecting dating biases or errors affecting conclusions and interpretations about the dating consistency of earliest memories. Finally, memory qualities of earliest memories displayed a high level of consistency with a two-year time lag regardless of remembering the same versus different event.


Experiences and Outcomes of Transition from Pediatric to Adult Health Care Services for Young People with Congenital Heart Disease: A Systematic Review.
This review synthesizes the empirical literature on outcomes and experiences of transfer and transition from pediatric to adult care for young people with congenital heart disease. A systematic review of papers published between January 2001 and May 2013 that examined outcomes or experiences of transfer and transition among young people with congenital heart disease was conducted. Data were extracted by two independent reviewers with the outcomes data combined using narrative synthesis and the experiences data integrated using thematic synthesis. Thirteen papers were included in the review: six reported outcomes following transfer, six reported experiences of transfer and transition, and one reported both outcomes and experiences. The review data indicate that high proportions of young people were lost to follow-up or experienced long gaps in care after leaving pediatric cardiology. Factors that protected against loss to follow-up or lapse in care included: beliefs that specialized adult care was necessary; poorer health status; attendance at pediatric appointments without parents; and pediatric referral to an adult congenital heart disease center. Data on experiences highlighted that many young people were unconcerned about transition, but lacked knowledge about their condition and were insufficiently prepared for transfer. In terms of adult services, many young people desired continuity in the quality of care, youth-oriented facilities, a personalized approach, and for their parents to remain involved in their care, but in a secondary, supportive capacity. In conclusion, the high proportions of young people lost to follow-up highlight the need for formal transition programs, which ensure a planned and coordinated transfer. Patients with congenital heart disease need education throughout adolescence about the implications of their condition, the differences between pediatric and adult services, and self-care management.


A cross-sectional study of parental awareness of and reasons for lack of health insurance among minority children, and the impact on health, access to care, and unmet needs.
Minority children have the highest US uninsurance rates; Latino and African-American children account for 53 % of uninsured American children, despite comprising only 48 % of the total US child population. The study aim was to examine parental awareness of and the reasons for lacking health insurance in Medicaid/CHIP-eligible minority children, and the impact of the children's uninsurance on health, access to care, unmet needs, and family financial burden. For this cross-sectional study, a consecutive series of uninsured, Medicaid/CHIP-eligible Latino and African-American children was recruited at 97 urban Texas community sites, including supermarkets, health fairs, and schools. Measures/outcomes were assessed using validated instruments, and included sociodemographic characteristics, uninsurance duration, reasons for the child being uninsured, health status, special healthcare needs, access to medical and dental care, unmet needs, use of health services, quality of care, satisfaction with care, out-of-pocket costs of care, and financial burden. The mean time uninsured for the 267 participants was 14 months; 5 % had never been insured. The most common reason for insurance loss was expired and never reapplied (30 %), and for never being insured, high insurance costs. Only 49 % of parents were aware that their uninsured child was Medicaid/CHIP eligible. Thirty-eight percent of children had suboptimal health, and 2/3 had special healthcare needs, but 64 % have no primary-care provider; 83 % of parents worry about their child's health more than others. Unmet healthcare needs include: healthcare, 73 %; mental healthcare, 70 %; mobility aids/devices, 67 %; dental, 61 %; specialty care, 57 %; and vision, 46 %. Due to the child's health, 35 % of parents had financial problems, 23 % cut work hours, and 10 % ceased work. Higher proportions of Latinos lack primary-care providers, and higher proportions of African-Americans experience family financial burden. Half of parents of uninsured minority children are unaware that their children are Medicaid/CHIP-eligible. These uninsured children have suboptimal health, impaired access to care, and major unmet needs. The child's health causes considerable family financial burden, and one in 10 parents ceased work. The study findings indicate urgent needs for better parental education about Medicaid/CHIP, and for improved Medicaid/CHIP outreach and enrollment.


Combined Experimental Approach and Finite Element Modeling of Small Molecule Transport Through Joint Synovium to Measure Effective Diffusivity.
Trans-synovial solute transport plays a critical role in the clearance of intra-articularly (IA) delivered drugs. In this study, we present a computational finite element model (FEM) of solute transport through the synovium validated by experiments on synovial explants. Unsteady diffusion of urea, a small uncharged molecule, was measured through devitalized porcine and human synovium using custom-built diffusion chambers. A multiphasic computational model was constructed and optimized with the experimental data to extract effective diffusivity for urea within the synovium. A monotonic decrease in urea concentration was observed in the donor bath over time, with an effective diffusivity found to be an order of magnitude lower in synovium versus that measured in free solution. Parametric studies incorporating an intimal cell layer with varying thickness and varying effective diffusivities were performed, revealing a dependence of drug clearance kinetics on both parameters. The findings of this study indicate that the synovial matrix impedes urea solute transport out of the joint with little retention of the solute in the matrix.


Behavioral responses of one western lowland gorilla (Gorilla gorilla gorilla) group at Bai Hokou, Central African Republic, to tourists, researchers and trackers.
Gorilla tourism, widely perceived as a lucrative industry, is propelled by strong market demand with programs in five countries and for three of four gorilla subspecies. Human presence may negatively affect wild gorillas, potentially lowering immunity and increasing the likelihood of acquiring human-borne disease. Yet, behavioral impacts of humans on wild gorilla behavior remain largely unexplored, particularly for western lowland gorillas. We evaluate the impact of tourist presence, human observer numbers (tourists, trackers, and researchers), and human observer distance on the behavior of one habituated gorilla group at Bai Hokou, Central African Republic. Behavioral data were collected for more than 12 months from January 2007. Of silverback aggressive events, 39% (N=229) were human directed, but 65% were low-level soft barks. Adult females, and one in particular, were responsible for the highest number of aggressive events toward humans. Humans maintained closer proximity to the silverback when tourists were present, although tourist numbers had no significant impact on overall group activity budgets or rates of human-directed aggression. However, as research team size increased, group feeding rates decreased. Close observer-silverback distance correlated with a decrease in his feeding rates and an increase in human monitoring. He directed less aggression toward observers at distances >10 m, although observers spent 48.5% of time between 6 and 10 m of the silverback. We discuss gorilla personality as a factor in human-directed aggression. We explore whether the current 7 m distance limit governing gorilla tourism, based on disease transmission risks, is sufficient considering the potential behavioral stressor of close human presence. We recommend increasing minimum observation distance to >10 m where possible, decreasing observer group sizes, particularly after a visit consisting of maximum numbers and restricting tourist access to 1 visit/day.


Phylogeographic patterns in Drosophila montana.
The Drosophila virilis species group offers valuable opportunities for studying the roles of chromosomal re-arrangements and mating signals in speciation. The 13 species are divided into two subgroups, the montana and virilis 'phylads'. There is greater differentiation among species within the montana phylad in both karyotype and acoustic signals than exists among members of the virilis phylad. Drosophila montana is a divergent species which is included in the montana phylad. Here, we analyse the phylogeography of D. montana to provide a framework for understanding divergence of acoustic signals among populations. We analysed mitochondrial sequences corresponding to the cytochrome oxidase I and cytochrome oxidase II genes, as well as 16 microsatellite loci, from 108 lines of D. montana covering most of the species' range. The species shows a clear genetic differentiation between North American and Scandinavian populations. Microsatellite allele frequencies and mitochondrial DNA haplotypes gave significant FST values between populations from Canada, USA and Finland. A Bayesian analysis of population structure based on the microsatellite frequencies showed four genetically distinct groups, corresponding to these three populations plus a small sample from Japan. A network based on mitochondrial haplotypes showed two Finnish clades of very different shape and variability, and another clade with all sequences from North America and Japan. All D. montana populations showed evidence of demographic expansion but the patterns inferred by coalescent analysis differed between populations. The divergence times between Scandinavian and North American clades were estimated to range from 450,000 to 900,000 years with populations in Canada and the USA possibly representing descendants of different refugial populations. Long-term separation of D. montana populations could have provided the opportunity for differentiation observed in male signal traits, especially carrier frequency of the song, but relaxation of sexual selection during population expansion may have been necessary.


Frequency of acute longus colli tendinitis on CT examinations.
We attempted to determine the frequency of acute longus colli tendinitis on diagnostic CT imaging performed at a large multicenter health care system. By correlating with the pre-imaging clinical information, we investigated which patient presentations should lead the radiologist to increased suspicion for this condition. Images from a total of 8101 adult CT examinations of the neck and cervical spine performed over a 3-month period were evaluated by researchers independent of the original clinical report. Clinical information available at the time of imaging was reviewed and assigned to one of five categories. Frequency of the condition was calculated by sex and clinical presentation. This retrospective study with waiver of consent and waiver of HIPPA was approved by our IRB. Nine positive scans were found for an overall frequency of 1.1 per 1000 examinations. The frequency was significantly higher (11.4 per thousand) on scans performed of patients presenting without history of recent trauma, concern for tumor, suspected postoperative complication, or clinical signs of infection localized to the neck. Although frequency in males was higher than in females, this did not reach statistical significance. In no positive or negative case was longus colli tendinitis considered in the pre-imaging documentation. Findings of acute longus colli tendinitis on CT examination generally occur in the absence of prior mention of this condition in the medical record. The radiologist should be particularly alert for this diagnosis when a patient presents with rapid-onset neck pain without a clear history of recent trauma or other etiologies.


Acute respiratory illness and return to sport: a systematic review and meta-analysis by a subgroup of the IOC consensus on 'acute respiratory illness in the athlete'.
To determine the days until return to sport (RTS) after acute respiratory illness (ARill), frequency of time loss after ARill resulting in >1 day lost from training/competition, and symptom duration (days) of ARill in athletes. Systematic review and meta-analysis. PubMed, EBSCOhost, Web of Science, January 1990-July 2020. Original research articles published in English on athletes/military recruits (15-65 years) with symptoms/diagnosis of an ARill and reporting any of the following: days until RTS after ARill, frequency (%) of time loss >1 day after ARill or symptom duration (days) of ARill. 767 articles were identified; 54 were included (n=31 065 athletes). 4 studies reported days until RTS (range: 0-8.5 days). Frequency (%) of time loss >1 day after ARill was 20.4% (95% CI 15.3% to 25.4%). The mean symptom duration for all ARill was 7.1 days (95% CI 6.2 to 8.0). Results were similar between subgroups: pathological classification (acute respiratory infection (ARinf) vs undiagnosed ARill), anatomical classification (upper vs general ARill) or diagnostic method of ARinf (symptoms, physical examination, special investigations identifying pathogens). In 80% of ARill in athletes, no days were lost from training/competition. The mean duration of ARill symptoms in athletes was 7 days. Outcomes were not influenced by pathological or anatomical classification of ARill, or in ARinf diagnosed by various methods. Current data are limited, and future studies with standardised approaches to definitions, diagnostic methods and classifications of ARill are needed to obtain detailed clinical, laboratory and specific pathogen data to inform RTS. CRD42020160479.


Quantitative real-time PCR tests for diagnostic and prognostic purposes in cases of legionellosis.
The usefulness of two quantitative real-time PCR assays (qrt-PCRmip targeting Legionella pneumophila, and qrt-PCR16S targeting all Legionella species) performed on lower respiratory tract (LRT) samples for diagnostic and prognostic purposes in 311 patients hospitalized for community-acquired pneumonia (CAP) in Rhône-Alpes (France) was evaluated. The Now Legionella urinary antigen test (UAT) from Binax (Portland, ME, USA) was used as a reference test. Samples were divided into two groups. Group A included 255 CAP patients admitted to Chambery hospital in 2005 and 2006. The Now Legionella UAT was positive in 14 patients. Sensitivities, specificities, positive predictive and negative predictive values for both qrt-PCR tests were 63.6, 98.7, 77.7 and 97.4%, respectively. Group B included 56 consecutive legionellosis patients diagnosed during a 4-year period (2003-2006) at the Grenoble University Hospital. The qrt-PCR16S and qrt-PCRmip displayed a sensitivity of 82.14 and 80.4%, respectively. Among the 70 legionellosis cases, L. pneumophila serogroup 1 was isolated in 15; qrt-PCRmip was positive in another 36, suggesting L. pneumophila infection, whereas the Legionella species involved could not be determined in the remaining 19 cases. The Legionella burden in LRT samples at the time of admission was determined in 46 patients using qrt-PCR16S tests, 44 for qrt-PCR mip groups A and B patients. It varied from 1.9 to 8.35 log(10) DNA copies/mL of LRT sample for qrt-PCR16S and from 1.9 to 8.11 log(10) DNA copies/mL of sample for qrt-PCRmip. High bacterial loads in LRT samples at hospital admission were significantly associated with higher Fine classes, the need for hospitalization in an intensive care unit and for prolonged hospitalization.


Regulatory properties of adenosine triphosphate-L-methionine S-adenosyltransferase of rat liver.
1. Double-reciprocal plots of the reaction velocity of yeast, rat liver and Escherichia coli ATP-l-methionine S-adenosyltransferases (EC 220.127.116.11) as a function of the l-methionine concentrations (under saturating ATP conditions) demonstrate downward deflexions from linearity for the yeast and E. coli adenosyltransferases and an upward deflexion for the rat liver enzyme. 2. The activities of partially purified preparations of rat liver ATP-l-methionine S-adenosyltransferase are enhanced by low concentrations of non-substrate analogues of l-methionine [e.g. 1-aminocyclopentanecarboxylic acid (cycloleucine) and l-2-amino-4-hexynoic acid], or by inorganic tripolyphosphate, an ATP analogue. When the concentrations of these analogues were raised further, the activity decreased. Double-reciprocal plots became linear in the presence of these modifier analogues. The inhibitions are common to all the l-methionine adenosyltransferases examined, but the activation(s) were only found with rat and mouse liver enzymes and not with enzymes obtained from several other tissues of these or other species. 3. The rate of formation of S-adenosyl-l-methionine bears a sigmoidal relation to the l-methionine concentrations when ATP is saturating. The activating effects of the l-methionine analogues and of tripolyphosphate are observed at low l-methionine concentrations, and become obliterated as the l-methionine concentration is raised. These findings are analysed in terms of various regulatory enzyme models.


Dispersers shape fruit diversity in Ficus (Moraceae).
Seed dispersal by vertebrates is one of the most common and important plant-animal mutualisms, involving an enormous diversity of fruiting plants and frugivorous animals. Even though plant reproduction depends largely on seed dispersal, evolutionary ecologists have been unable to link co-occurring traits in fruits with differences in behavior, physiology, and morphology of fruit-eating vertebrates. Hence, the origin and maintenance of fruit diversity remains largely unexplained. Using a multivariate phylogenetic comparative test with unbiased estimates of odor and color in figs, we demonstrate that fruit traits evolve in concert and as predicted by differences in the behavior, physiology (perceptive ability) and morphology of their frugivorous seed dispersers. The correlated evolution of traits results in the convergence of general appearance of fruits in species that share disperser types. Observations at fruiting trees independently confirmed that differences in fig traits predict differences in dispersers. Taken together, these results demonstrate that differences among frugivores have shaped the evolution of fruit traits. More broadly, our results underscore the importance of mutualisms in both generating and maintaining biodiversity.


The giant cell tumour of the proximal phalanx of the thumb treated by a 2-stage operation.
We present a 29-year-old woman who was treated for a giant-cell tumour of her thumb. Surgical treatment was performed in two stages. In the first stage, the tumour was removed and the first metacarpal and distal phalanges were fixed by an external fixator. In the second stage of reconstruction of the thumb, a cortico-cancellous bone graft from the iliac crest, an external fixator and double arthrodesis were used. This two-stage procedure provides the possibility for confirming the diagnosis and appropriate treatment choice and minimizes the risk of recurrence.


Long-term conceptual implicit memory: a decade of evidence.
Demonstrations of long-term implicit memory are numerous, but to date they have been reported in what might be thought of as perceptually driven tasks. In the present experiment, a low-frequency U.S. state name was presented verbally to participants within the context of a memory-course lecture, and the influence of that experience was measured indirectly 4 to 8 weeks later using a state-name-generation task. Participants were significantly more likely to generate the critical state name when it had been presented in an earlier lecture than when it had not been presented in an earlier lecture, a novel demonstration of long-term, conceptually driven priming after a single stimulus exposure.


Contra-IL 2; a suppressor lymphokine that inhibits IL 2 activity.
Suppressive activity of culture supernatant of AS-9 (AS-9 CS), a T cell hybridoma line that was derived from fusion of BW5147 thymoma and splenic T cells of anti-lymphocyte serum-treated C3H mice, was analyzed. AS-9 CS inhibited allogeneic cytotoxic T lymphocyte (CTL) generation as well as T cell proliferation to alloantigens and mitogens, but failed to inhibit B cell response to lipopolysaccharide or growth of tumor and fibroblast cells. Although addition of AS-9 CS to the allogeneic sensitization culture as late as on day 2 of incubation resulted in maximal inhibiton of CTL generation, removal of AS-9 CS on day 3 of incubation abolished its inhibitory effect. Addition of purified IL 2 together with AS-9 CS to the allogeneic sensitization cultures only partially abrogated the suppression. Experiments with IL 2-dependent cytotoxic T cell line (CTLL) showed that AS-9 CS suppressed the IL 2-induced proliferation of CTLL. Preincubation of AS-9 CS with CTLL removed its inhibitory effect on CTL generation. These results indicate that AS-9 CS interferes with the mechanism of T cell activation by IL 2. On this basis, AS-9 CS was named contra-IL 2.


Candidate driver genes in microsatellite-unstable colorectal cancer.
Defects in the mismatch repair system lead to microsatellite instability (MSI), a feature observed in ∼ 15% of all colorectal cancers (CRCs). Microsatellite mutations that drive tumourigenesis, typically inactivation of tumour suppressors, are selected for and are frequently detected in MSI cancers. Here, we evaluated somatic mutations in microsatellite repeats of 790 genes chosen based on reduced expression in MSI CRC and existence of a coding mononucleotide repeat of 6-10 bp in length. All the repeats were initially sequenced in 30 primary MSI CRC samples and whenever frameshift mutations were identified in >20%, additional 70 samples were sequenced. To distinguish driver mutations from passengers, we similarly analyzed the occurrence of frameshift mutations in 121 intronic control repeats and utilized a statistical regression model to determine cut-off mutation frequencies for repeats of all types (A/T and C/G, 6-10 bp). Along with several know target genes, including TGFBR2, ACVR2, and MSH3, six novel candidate driver genes emerged that harbored significantly more mutations than identical control repeats. The mutation frequencies in 100 MSI CRC samples were 51% in G8 of GLYR1, 47% in T9 of ABCC5, 43% in G8 of WDTC1, 33% in A8 of ROCK1, 30% in T8 of OR51E2, and 28% in A8 of TCEB3. Immunohistochemical staining of GLYR1 revealed defective protein expression in tumors carrying biallelic mutations, supporting a loss of function hypothesis. This is a large scale, unbiased effort to identify genes that when mutated are likely to contribute to MSI CRC development.


A 3D navigation template for guiding a unilateral lumbar pedicle screw with contralateral translaminar facet screw fixation: a study protocol for multicentre randomised controlled trials.
The incidence of lumbar disc degeneration disease has increased in recent years. Lumbar interbody fusion using two unilateral pedicle screws and a translaminar facet screw fixation has advantages of minimal invasiveness and lower costs compared with the traditional methods. Moreover, a method guided by a three-dimensional (3D) navigation template may help us improve the surgical accuracy and the success rate. This is the first randomised study using a 3D navigation template to guide a unilateral lumbar pedicle screw with contralateral translaminar facet screw fixation. Patients who meet the criteria of the surgery will be randomly divided into experimental groups and control groups by a computer-generated randomisation schedule. We will preoperatively design an individual 3D navigation template using CATIA software and MeditoolCreate. The following primary outcomes will be collected: screw angles compared with the optimal screw trajectories in 3D digital images, length of the wound incision, operative time, intraoperative blood loss and complications. The following secondary outcomes will be collected: visual analogue scale (VAS) for back pain, VAS for leg pain and the Oswestry Disability Index. These parameters will be evaluated on day 1 and then 3, 6, 12 and 24 months postoperatively. The study has been reviewed and approved by the institutional ethics review board of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University. The results will be presented at scientific communities and peer-reviewed journals. ChiCTR-IDR-17010466.


Optic neuritis in children.
To describe the clinical characteristics of optic neuritis in children, including final visual acuity and development of multiple sclerosis (MS). Charts were reviewed of all patients < 15 years of age who presented with optic neuritis to the Bascom Palmer Eye Institute or the Miami Children's Hospital between 1986 and 1998. Fifteen patients were identified. There was a slight female predilection in the study group (60%), with a mean age of 9.8 years at presentation. A preceding febrile illness within 2 weeks of visual symptoms was reported in 66% of patients. Initial visual acuity ranged from 20/15 to no light perception. Involvement was bilateral in 66% of patients, and disc swelling was present in 64% of involved eyes. Of the patients who underwent magnetic resonance imaging, 33% had focal demyelinating lesions in the brain, and 63% of affected nerves were enlarged or enhanced with gadolinium. Eleven patients were treated with intravenous steroids. Final visual acuity was > or = 20/40 in 58.3% of eyes. Thirty percent of the patients had vision of finger counting or worse. Four (26%) patients developed MS. The mean age of patients with MS was 12 years, compared with 9 years in children who did not develop MS. Patients with unilateral involvement had an excellent visual prognosis (100% > 20/40), but a higher rate of development of MS (75%). Two patients had positive serology for Lyme disease. Optic neuritis presents differently in children than in adults. Children typically have bilateral involvement with papillitis following an antecedent viral illness. Although visual prognosis is poorer in children than adults, the development of MS is less common in children. Children who present with unilateral involvement have a better visual prognosis; however, they also develop MS at a greater frequency than children with bilateral involvement. Patients who developed MS were, on average, older at presentation with optic neuritis than those who did not develop MS.


Brain metastasis-initiating cells: survival of the fittest.
Brain metastases (BMs) are the most common brain tumor in adults, developing in about 10% of adult cancer patients. It is not the incidence of BM that is alarming, but the poor patient prognosis. Even with aggressive treatments, median patient survival is only months. Despite the high rate of BM-associated mortality, very little research is conducted in this area. Lack of research and staggeringly low patient survival is indicative that a novel approach to BMs and their treatment is needed. The ability of a small subset of primary tumor cells to produce macrometastases is reminiscent of brain tumor-initiating cells (BTICs) or cancer stem cells (CSCs) hypothesized to form primary brain tumors. BTICs are considered stem cell-like due to their self-renewal and differentiation properties. Similar to the subset of cells forming metastases, BTICs are most often a rare subpopulation. Based on the functional definition of a TIC, cells capable of forming a BM could be considered to be brain metastasis-initiating cells (BMICs). These putative BMICs would not only have the ability to initiate tumor growth in a secondary niche, but also the machinery to escape the primary tumor, migrate through the circulation, and invade the neural niche.


Geographic patterns of prostate cancer mortality and variations in access to medical care in the United States.
Striking geographic variation in prostate cancer death rates have been observed in the United States since at least the 1950s; reasons for these variations are unknown. Here we examine the association between geographic variations in prostate cancer mortality and regional variations in access to medical care, as reflected by the incidence of late-stage disease, prostate-specific antigen (PSA) utilization, and residence in rural counties. We analyzed mortality data from the National Center for Health Statistics, 1996 to 2000, and incidence data from 30 population-based central cancer registries from the North American Association of Central Cancer Registries, 1995 to 2000. Ecological data on the rate of PSA screening by registry area were obtained from the 2001 Behavioral Risk Factor Surveillance System. Counties were grouped into metro and nonmetro areas according to Beale codes from the Department of Agriculture. Pearson correlation analyses were used to examine associations. Significant correlations were observed between the incidence of late-stage prostate cancer and death rates for Whites (r = 0.38, P = 0.04) and Blacks (r = 0.53, P = 0.03). The variation in late-stage disease corresponded to about 14% of the variation in prostate cancer death rates in White men and 28% in Black men. PSA screening rate was positively associated with total prostate cancer incidence (r = 0.42, P = 0.02) but inversely associated with the incidence of late-stage disease (r = -0.58, P = 0.009) among White men. Nonmetro counties generally had higher death rates and incidence of late-stage disease and lower prevalence of PSA screening (53%) than metro areas (58%), despite lower overall incidence rates. These ecological data suggest that 10% to 30% of the geographic variation in mortality rates may relate to variations in access to medical care.


[Performance diagnosis of the locomotor system and sensory organs?].
The quantitative significance of the sensory organs in sport is discussed by means of the visual parameters static and dynamic visual acuity and the equilibrium that is specific for a particular kind of sport. Spectators with normal visual acuity can identify footballs, tennis balls etc. used in game sports, with relative ease, compared with sports equipment used in athletics. However, since moving objects can attain an angular velocity of 400 degrees/s and higher in certain sports, the mean dynamic visual acuity is unable to cope with such speeds, this being only 200 to 230 degrees/s. Dynamic visual acuity can be trained, thus attaining higher levels in game sports. Processes of balance regulation during cycling (or in rhythmical sports gymnastics) are discussed in connection with and subsequent to the problem of the intersensory perception conflict. Finally, the article sums up criteria for the observation of movement and for minimising intersensory perception conflicts.


UGE1 and UGE2 regulate the UDP-glucose/UDP-galactose equilibrium in Cryptococcus neoformans.
The genome of the basidiomycete pathogenic yeast Cryptococcus neoformans carries two UDP-glucose epimerase genes (UGE1 and UGE2). UGE2 maps within a galactose cluster composed of a galactokinase homologue gene and a galactose-1-phosphate uridylyltransferase. This clustered organization of the GAL genes is similar to that in most of the hemiascomycete yeast genomes and in Schizosaccharomyces pombe but is otherwise not generally conserved in the fungal kingdom. UGE1 has been identified as necessary for galactoxylomannan biosynthesis and virulence. Here, we show that UGE2 is necessary for C. neoformans cells to utilize galactose as a carbon source at 30 degrees C but is not required for virulence. In contrast, deletion of UGE1 does not affect cell growth on galactose at this temperature. At 37 degrees C, a uge2Delta mutant grows on galactose in a UGE1-dependent manner. This compensation by UGE1 of UGE2 mutation for growth on galactose at 37 degrees C was not associated with upregulation of UGE1 transcription or with an increase of the affinity of the enzyme for UDP-galactose at this temperature. We studied the subcellular localization of the two enzymes. Whereas at 30 degrees C, Uge1p is at least partially associated with intracellular vesicles and Uge2p is on the plasma membrane, in cells growing on galactose at 37 degrees C, Uge1p colocalizes with Uge2p to the plasma membrane, suggesting that its activity is regulated through subcellular localization.


An application of multidimensional time-frequency analysis as a base for the unified watermarking approach.
A watermarking approach based on multidimensional time-frequency analysis is proposed. It represents a unified concept that can be used for different types of data such as audio, speech signals, images or video. Time-frequency analysis is employed for speech signals, while space/spatial-frequency analysis is used for images. Their combination is applied for video signals. Particularly, we focus on the 2-D case: space/spatial-frequency based image watermarking procedure that will be subsequently extended to video signal. A method that selects coefficients for watermarking by estimating the local frequency content is proposed. In order to provide watermark imperceptibility, the nonstationary filtering is used to model the watermark which corresponds to the host signal components. Furthermore, the watermark detection within the multidimensional time-frequency domain is proposed. The efficiency and robustness of the procedure in the presence of various attacks is proven experimentally.


Neuronal and glial localization of GAT-1, a high-affinity gamma-aminobutyric acid plasma membrane transporter, in human cerebral cortex: with a note on its distribution in monkey cortex.
High-affinity gamma-aminobutyric (GABA) plasma membrane transporters (GATs) influence the action of GABA, the main inhibitory neurotransmitter in the human cerebral cortex. In this study, the cellular expression of GAT-1, the main cortical GABA transporter, was investigated in the human cerebral cortex by using immunocytochemistry with affinity-purified polyclonal antibodies directed to the C-terminus of rat GAT-1. In temporal and prefrontal association cortex (Brodmann's areas 21 and 46) and in cingulofrontal transition cortex (area 32), specific GAT-1 immunoreactivity (ir) was localized to numerous puncta and fibers in all cortical layers. GAT-1+ puncta were distributed homogeneously in all cortical layers, although they were slightly more numerous in layers II-IV, and appeared to have a preferential relationship to the somata and proximal dendrites of unlabeled pyramidal cells, even though, in many cases, they were also observed around nonpyramidal cells. Electron microscopic observations showed that GAT-1+ puncta were axon terminals that formed exclusively symmetric synapses. In addition, some distal astrocytic processes also contained immunoreaction product. Analysis of the patterns of GAT-1 labeling in temporal and prefrontal association areas (21 and 46), in cingulofrontal transition areas (32), and in somatic sensory and motor areas (1 and 4) of the monkey cortex revealed that its distribution varies according to the type of cortex examined and indicated that the distribution of GAT-1 is similar in anatomically corresponding areas of different species. The present study demonstrates that, in the human homotypical cortex, GAT-1 is expressed by both inhibitory axon terminals and astrocytic processes. This localization of GAT-1 is compatible with a major role for this transporter in GABA uptake at GABAergic synapses and suggests that GAT-1 may contribute to determining GABA levels in the extracellular space.


Prehospital consideration of sildenafil-nitrate interactions.
To determine whether paramedics and on-line physicians screen patients for use of sildenafil citrate (Viagra) prior to prehospital administration of nitrates. A prospective, observational study was performed over a one-month period in three EMS systems. Consecutive radio communications between on-line physicians and paramedics concerning male patients with cardiac complaints were monitored. Investigators observed the frequency with which on-line physicians screened for sildenafil use prior to ordering nitrates. After observation of the radio communications was completed, a written survey was distributed to all paramedics in the three EMS systems. Seventy-six physician-paramedic interactions were monitored. Nitrates were ordered by on-line physicians in 56 cases. No paramedic reported sildenafil use/nonuse, and no on-line physician inquired about the patient's potential use of the drug. Only half of the surveyed paramedics reported that they routinely screen for sildenafil use, and approximately a fourth reported that its use would not alter their management of chest pain patients. In this study, on-line physicians in three EMS settings did not screen for sildenafil use prior to ordering nitrates. While some paramedics do screen for sildenafil use, practice patterns among paramedics in these three systems were inconsistent.


Assessment of the feed additive consisting of Lactococcus lactis DSM 11037 for all animal species for the renewal of its authorisation (Chr. Hansen A/S).
Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application for renewal of Lactococcus lactis DSM 11037, a technological additive to improve ensiling of forage for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing conditions of authorisation. There is no new evidence that would lead the FEEDAP Panel to reconsider its previous conclusions. Thus, the Panel concludes that the additive remains safe for all animal species, consumer and the environment under the authorised conditions of use. Regarding user safety, the additive is not a skin and eye irritant but should be considered a respiratory sensitiser. In absence of data, the Panel cannot conclude on the skin sensitisation potential of the additive. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.


Feelings of Women With Strong Family Histories Who Subsequent to Their Breast Cancer Diagnosis Tested BRCA Positive.
Family physicians in Canada as reported in several studies do not recognize the importance of family history in relation to breast/ovarian cancer and thus Canadian women with strong family histories continue to develop early-onset breast cancer without the knowledge of or ability to make choices regarding increased surveillance or preventative strategies. This study explored the feelings of women who learned about their hereditary risk only after their diagnosis younger than 52 years and who eventually tested positive for a BRCA gene mutation. Thirty-four such women were mailed an invitation to participate in this research including a letter of information, consent form, and discussion prompts for their written narrative response. Rigorous mixed method analyses were performed using Charmaz-based qualitative analyses as well as quantitative analyses. Thirteen women (38.2%) responded with narratives for qualitative analysis from which 4 themes were coconstructed as follows: I, types of emotions; II, emotional response; III, coping with emotions; and IV, advice to women at similar risk. Women felt they should have learned about their hereditary risk from their family physician and through public education before their diagnosis. Although not experienced at the time of diagnosis, anger, frustration, and regret were experienced after receiving their BRCA results. These emotions arose from our research participants' lack of opportunity for prior genetic counseling and testing opportunity for genetic counseling and testing. With increased public and physician education, it is hoped that women with significant family histories of breast/ovarian cancer will be identified before diagnosis and given options regarding cancer surveillance and risk reduction strategies.


Hypoxic-ischemic injury induces monocyte chemoattractant protein-1 expression in neonatal rat brain.
Monocyte chemoattractant protein-1 (MCP-1) regulates monocyte accumulation in several macrophage-dependent experimental disease models. In the neonatal brain, activated microglia accumulate rapidly after hypoxic-ischemic injury. These cells produce potentially neurotoxic factors that may contribute to the progression of injury. To determine whether MCP-1 could be one of the molecular signals that influences the microglial response to hypoxic-ischemic injury in the neonatal brain, we examined the impact of acute hypoxic-ischemic injury on MCP-1 mRNA and protein expression. Seven-day-old rats underwent right carotid artery ligation, followed by 3 hours of 8% oxygen exposure, to elicit ipsilateral forebrain hypoxic-ischemic injury. To detect MCP-1 mRNA in situ hybridization assays were performed using 35S-labeled antisense riboprobes generated from rat MCP-1 cDNA. Animals were evaluated 0, 1, 2, 4, 8, 16, 24, 48, and 120 hours after hypoxic exposure (N > or = 3/group). Immunocytochemistry (with a polyclonal rabbit antirat MCP-1 antibody) was used to determine the anatomic and temporal distribution of MCP-1, in samples obtained 10 minutes to 5 days after hypoxic exposure (N > or = 3/group). Monocyte chemoattractant protein-1 mRNA was first detected in periventricular regions of the lesioned hemisphere 1 hour after hypoxia-ischemia; periependymal and intraparenchymal MCP-1 mRNA expression were detected at 4 hours; hybridization signal peaked at 8 to 24 hours; and no MCP-1 mRNA was detected at 48 and 120 hours. In lesioned forebrain, MCP-1 protein expression were consistently detected at 2.5 to 48 hours after hypoxia-ischemia. Many immunoreactive cells appeared to be neurons. These results suggest that in the developing brain, MCP-1 could represent a functionally important molecular signal for the microglial response to hypoxic-ischemic injury.